Regioselective and stereospecific azidation of 1,2-and 1,3-diols by azidotrimethylsilane via a Mitsunobu reaction

A one-pot regio- and stereospecific azidation reaction of 1,2- and 1,3-diol s with azidotrimethylsilane (Me3SiN3) via a Mitsunobu reaction has been ach ieved. With 1,2- and 1,3-diols, the reaction of triphenylphosphine, diisopr opyl azodicarboxylate, and Me3SiN3 in dichloromethane gave regioselective a zidation at C-2 and C-3, respectively, in good yield (74-90% combined yield of 1a + 1b or of 2a + 2b). However, application of the same reaction condi tions to a 1,4-diol led to the exclusive formation of the cyclic ether. The regioselectivity of this one-pot reaction is influenced by the solvent, th e degree of steric bulk at C-2 of the 1,2-diol or at C-3 of the 1,3-diol, a nd the presence of electron-donating and electron-withdrawing groups near t he secondary carbinol carbon. This selectivity is discussed in terms of the mechanistic model proposed by Mathieu-Pelta and Evans (Mathieu-Pelta, I.; Evans, S. A., Jr. J. Org. Chem. 1898, 57, 3409-3413), which involves reacti on of the dioxaphospholane intermediate with Me3SiN3 to form oxyphosphonium ions 4 and 5.